Capsule

ABSTRACT

The present invention relates to gelatin composite for the use of capsules to fill medicine and the like, coating agents or binding agents of tablets, casing materials and so on. A gelatin composite of the invention is characterized by comprising gelatin and polypeptide as an essential component, wherein the polypeptide is in the range of 15-70% by weight, referring to the total weight of the polypeptide and gelatin, and the gelatin has a gelly strength of 250 bloom or greater. The gelatin composite prevents insolubilization of the gelatin due to the passage of time without any degradation of shape-retaining ability of the gelatin composite.

DESCRIPTION

1. Technical Field

This invention relates to gelatin composite for the use of capsules tofill medicine and the like, coating agents or binding agents of tablets,casing materials and so on.

2. Background Art

Some medicines, for example, are cased in capsules to prepare capsulemedicines which are used with a purpose of easy taking or sureabsorption at the digestive organ destined. A capsule for such use isrequired to have a shape-retaining ability which can retain the shapeunder various conditions, and to show disintegration which does notchange with the passage of time.

The change of disintegration with the passage of time is said to becaused by that the gelatin, a main component of the capsule, reacts bythemselves or with a substance enclosed in the capsule, and becomesinsoluble as the time passes.

Japanese Patent Gazette (Kokai) No. 58-62120 discloses a soft capsule,which can prevent that kind of insolubilization of gelatin with thepassage of time. The soft capsule is a gelatin composite comprisingaddition of polypeptide of 0.5-10% by weight of the gelatin. The softcapsule was devised to prevent the insolubilization by allowing theadded polypeptide to react with an enclosed substance before gelatinreacts.

However, it was found by experiments of the present inventors that, in acase of that the substance enclosed is highly reactive, the amount ofpolypeptide consumption with the reaction seriously increase resultingin an unsufficient prevention of the insolubilization with the use ofamount in the above range. Then, if polypeptide is added over the rangeto solve the unsufficient prevention, it turns out to lead todegradation of the shape-retaining ability of the gelatin composite orthe products comprising it.

Considering these situations, the present invention was undertaken toprovide gelatin composite which can prevent the insolubilization ofgelatin due to the passage of time without any degradation of theshape-retaining ability of gelatin composite.

DISCLOSURE OF INVENTION

The invention provides a gelatin composite characterized by comprisinggelatin and polypeptide as an essential component, wherein thepolypeptide is in the range of 15-70% by weight, referring to the totalweight of the polypeptide and gelatin, and the gelatin has a gellystrength of 250 bloom or greater.

Below is the detailed description of the invention.

Gelatin composite of this invention comprises gelatin and polypeptide asan essential component. Besides the two, the gelatin composite may beadded with one or more of plasticizer, thickener, agent for coloring,etc. Some examples of the plasticizer are glycerin and sorbitol, andthey may be employed solely or in combination. Some examples ofthickener are gum arabic and alginic acid, and they may be employedsolely or in combination. Some examples of agents for coloring arevarious food colors, and they may be employed solely or in combination.

Gelatin used in the invention is required to have a gelly strength of250 bloom or greater. That is because, if the strength is below than 250bloom, the shape-retaining ability of gelatin composite or productscomprising it degrades even though the amount of the added polypeptideis relatively small. Herein the gelly strength was tested in accordancewith JIS K 6503 (1977 edition).

Gelatin may be produced under mild conditions preventing any degradationfactor of its gelly strength in order to keep a high gelly strength.However, it may be prepared in other methods, or obtained from themarket where gelatins having a gelly strength of 250 bloom or greaterare available.

The kind of polypeptide for the invention is not specialized. However,the polypeptide ratio should be here in the range of 15-70% by weight,referring to the total weight of the polypeptide and gelatin. Ifpolypeptide is added over the range, gelatin composite or productscomprising it may have a very low shape-retaining ability and will beunfavorable for practical use. If polypeptide is added under the range,the prevention effect on the insolubilization of gelatin with thepassage of time becomes unsufficient. This is also practicallyunfavorable.

Polypeptide to be employed in the invention is preferred to have amolecular weight of about 5000-10,000. Because under a molecular weightof 5000 the polypeptide may result in an undesiably low shape-retainingability, and over a molecular weight of 10,000, it may not preventeffectively the insolubilization of gelatin with the passage of time.

The insolubilization of gelatin with the passage of time is preventedefficiently because gelatin composite of this invention comprisespolypeptide. More specifically, that is because, when the gelatincomposite or products comprising it gets in touch with the reactingsubstance enclosed, the polypeptide chemically reacts with the substancebefore the gelatin does. Herein, the ratio of the polypeptide is in theabove-specified range so that, even if the touching substance is of ahigh reactivity, the lowering in solubility of the gelatin is preventedover a period of time, and the shape-retaining ability of productscomprising the gelatin composite does not decrease significantly.Besides, although the polypeptide is mixed in a large amount asdescribed above, the shape-retaining ability is maintained almost on thesame level as that of the products prepared by the existing gelatincomposite for capsules, because the subject gelatin has a gelly strengthof 250 bloom or greater.

Since gelatin composite of this invention is such as shown above, thedegree of insolubilization of gelatin in it with the passage of timebecomes small without any degradation of shape-retaining ability, andfurthermore, the degree of insolubilization with the passage of time issmall enough even when the gelatin composite come in contact with asubstance of high reactivity.

BEST MODE FOR CARRYING OUT THE INVENTION

Some examples of this invention will be explained in comparison withreferring examples which deviate from a range of numerical values ofthis invention. However, this invention is not limited to theseexamples. Polypeptides used in the following examples have molecularweights of about 8000.

EXAMPLES 1-5

According to the procedure shown in Table 1, sheets comprising thesubject gelatin composite were obtained by dissolving each group ofmaterials under warm conditions, mixing it well, cooling it down afterforming it into a sheet, and then drying it at a low temperature.

REFERENCE EXAMPLES 1-4

Dissolving under warm conditions followed by mixing was carried outaccording to the procedure shown in Table 1. Then, sheets comprising thecommon gelatin composite were obtained in the same method as the aboveexamples.

As to each of the examples 1-5 and reference examples 1-4, gellystrength was tested on the gelatin and on the mixture of gelatin andpolypeptide, and disintegration was tested on each sheet obtained.Results are shown in Table 1.

Gelly strength test was conducted in accordance with JIS K 6503 (1977edition).

Disintegration of sheets was tested on each of sheets obtainedimmediately after preparation, after a storage for six months at 40° C.,and after dipping in a liver oil for one month at 20° C. The testsresults were performed by determining time necessary for dissolution at37° C. with a disintegration apparatus. Results are shown in Table 1 bytime for dissolving 0.2 g of sheets.

                                      TABLE 1                                     __________________________________________________________________________    Composition of Aqueous                                                        Solution of Gelatin                                                                              Reference  Reference  Reference                                                                           Reference                      Composite and Physical                                                                      Example                                                                            Example                                                                             Example                                                                            Example                                                                             Example                                                                            Example                                                                             Example                                                                             Example                                                                            Example             Properties of Sheets                                                                        1    1     2    2     3    3     4     4    5                   __________________________________________________________________________    Components (g)                                                                Gelatin       70   70    80   90    35   25    92    50   50                  Polypeptide   30   30    20   10    65   75     8    50   50                  Glycerin      40   40    40   40    40   40    40    40   40                  Water         260  260   260  260   260  260   260   260  260                 Gelly Strength of                                                                           260  150   260  260   350  260   150   260  350                 Gelatin (bloom)                                                               Gelly Strength of Mixture                                                                   150  40    180  210   100  25    100   100  100                 of Gelatin and                                                                Polypeptide (bloom)                                                           Disintegration of                                                             Sheets (min.)                                                                 Immediately After                                                                            5    5     5   10     5    5    10     5    5                  Preparation                                                                   After storage for                                                                           10   *     10   24     5   *     24     5    5                  Six Months                                                                    After Dipping in                                                                            18   *     29   45    16   *     Insolu-                                                                             16   16                  Liver Oil for One                              bilized                        Month at 20° C.                                                        __________________________________________________________________________     *Sheets were too soft to test, indicating no shaperetaining ability.     

As shown in Table 1, among reference examples 1-4 deviating from therange of numerical values specified in the subject invention, referenceexamples 1 and 3 have no shape-retaining ability and reference example 2shows a large decrease in disintegration with the passage of time.Reference example 4 showed still large disintegration and wasinsolubilized with dipping in a liver oil. In contrast, all the examples1-5 show smaller values in disintegration with the passage of time thanthe reference examples 2 and 4 and also, were superior in disintegrationon testing immediately after preparation, after a storage for six monthsfollowing after the preparation, and after dipping in a liver oil forone month.

INDUSTRIAL APPLICABILITY

Gelatin composite of the invention may be applicable to gelatincomposite on a raw material stage, on a product stage and a medium stagebetween those, if it comprises gelatin and polypeptide in theabove-specified ratio and other components where necessary.

Some examples of gelatin composite on a raw material stage of thisinvention are a powder prepared by mixing gelatin and polypeptide in theabove-specified ratio, a powder prepared by mixing this powder withother materials where necessary, or a solution comprising such powders.

Examples of gelatin composite on a product stage of this invention arecapsules or microcapsules to enclose medicines or the like, casingmaterials in the form of sheet or film, or binding agents or coatingagents for tablets, etc.

In this invention, some examples of gelatin composite on a stage betweenthe raw material and product stages are sheets to form capsules, andsheets or films to form casing materials in a bag form or the like.

In the case that gelatin composite of the invention is led to capsules,capsules may be either a soft or a hard type, or a medium type betweenthose. They may take a form of microcapsule. Shape or scale is notlimited.

Though the capsules comprising gelatin composite in the invention aredifferent from prior capsules in a high gelly strength of gelatin and ina large ratio of polypeptide, they may be prepared by the existingmethods and equipments so far used in this field. Consequently, there isno need to make any new plant and equipment investment.

When capsules are prepared from the subject gelatin composite, theworking conditions for so far known capsules can be applied withoutmeaningful modification. For example, aqueous solution comprising thesubject gelatin and polypeptide in the above-specified ratio and, ifnecessary, other materials is prepared. The solution is dried to formsheet according to a usual method. Out of the sheet, capsules may beobtained with such a continuous method as filling of contents with arotary filling machine, or with Plate Method using the said sheet.Instead of preparing sheet in advance, capsules may be prepared by sucha method as Globex method wherein contents is filled together withproduction of capsules. Method of preparing capsules comprising thesubject gelatin composition does not have a special limitation.

Substances enclosed in capsules or microcapsules comprising the gelatincomposition are of various kinds and no limitation; for example,medicines, foods, etc. The enclosed substances are not limited to liquidmaterials.

Microcapsules employing the subject gelatin composite as a wall materialmay be obtained, for example, by preparing aqueous solution comprisingthe subject gelatin composite, adding in it one or more oily or solidcore materials, then mixing it, and the mixture being subjected to aspray drying.

Casing material comprising the subject gelatin composite may beobtained, for example, by preparing sheet consisting of the gelatincomposite and making it into the form of bag or the like. Such a casingmaterial may be used as an envelope of solid or oily mateials.

Coated film being composed of the subject gelatin composite, may beobtained with a liquid for smoothing, a liquid for coloring, and thelike, which are prepared, for example, by adding gelatin of thespecified gelly strength and polypeptide in the specified ratio togetheror separately, instead of the common gelatin material so far employed.The coated film may be obtained by coating such a solution on thesurface of tablets. Some examples of coatings are sugar coating, watersoluble coating and enteric-soluble film-coating.

In making use of the subject gelatin composite as a binding agent fortablets, a binding agent, for example, for condensed tablets may beprepared by adding gelatin of the specified gelly strength andpolypeptide in the specified ratio together or separately instead of thecommon gelatin, which is a binding agent in production of condensedtablets.

We claim:
 1. A capsule the wall material of which consists essentiallyof 85-30% by weight of gelatin having a gelly strength of 250 bloom orgreater, and 15-70% by weight of a polypeptide having a molecular weightof about 5,000-10,,000.